α-Synuclein Ubiquitination and Novel Therapeutic Targets for Parkinson's Disease

ISSN: 1996-3181 (Online)
ISSN: 1871-5273 (Print)


Volume 13, 10 Issues, 2014


Download PDF Flyer




CNS & Neurological Disorders - Drug Targets

Formerly: Current Drug Targets - CNS & Neurological Disorders

Aims & ScopeAbstracted/Indexed in

Ranking and Category:
  • 96th of 254 in Pharmacology & Pharmacy

Submit Abstracts Online Submit Manuscripts Online

Editor-in-Chief:
Stephen D. Skaper
Department of Pharmaceutical and Pharmacological Sciences
University of Padova
Padova
Italy


View Full Editorial Board

Subscribe Purchase Articles Order Reprints

Current: 2.702
5 - Year: 3.298

α-Synuclein Ubiquitination and Novel Therapeutic Targets for Parkinson's Disease

Author(s): Ruth Rott, Raymonde Szargel, Vered Shani, Sleman Bisharat and Simone Engelender

Affiliation: Department of Biochemistry, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Bat-Galim, Haifa 31096, Israel.

Abstract

Accumulation of α-synuclein is key to the pathogenesis of Parkinson's disease (PD), though the exact mechanisms involved in its toxicity are still subject to debate. Increased α-synuclein expression or reduced degradation may play a role in the proteotoxicity observed in PD. Here we review the mechanisms of α-synuclein ubiquitination by different E3 ubiquitin-ligases, and its degradation via the proteasome, autophagy and lysosomes. Activators of α- synuclein ubiquitination and degradation pathways represent a plausible strategy to decrease α-synuclein burden in the disease. Nevertheless, since proteasomes and autophagy might be impaired in the disease, and because proteolytic impairment causes the accumulation of monoubiquitinated α-synuclein and the formation of toxic inclusions, compounds that promote α-synuclein monoubiquitination should be used in concert with compounds that boost these proteolytic pathways. This combined approach may therefore ease the accumulation of α-synuclein in PD and may represent a promising new avenue for the development of novel treatments for the disease.

Keywords: α-synuclein, autophagy, Parkinson's disease, proteasome, SIAH (Seven in Absentia Homolog), ubiquitination, USP9X.

Purchase Online Order Reprints Order Eprints Rights and Permissions

  
  



Article Details

Volume: 13
Issue Number: 4
First Page: 630
Last Page: 637
Page Count: 8
DOI: 10.2174/18715273113126660195
Advertisement

Related Journals




Webmaster Contact: urooj@benthamscience.org Copyright © 2014 Bentham Science